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Acceleration of the refolding of Arc repressor by nucleic acids and other polyanions

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Abstract

The refolding rate of the Arc repressor dimer can be accelerated 30-fold or more by negatively charged polymers including single-stranded and double-stranded DNA, RNA, and polyvinylsulfate but not by neutral or positively charged polymers. The salt-dependence of the polyanion-mediated process and mutant studies indicate that electrostatic interactions are important in the rate acceleration. Urea-dependence studies suggest that Arc is relatively unstructured in the transition state for polyanion-stimulated refolding. At low ionic strength, the observed kinetics of refolding are consistent with a model in which denatured Arc monomers bind rapidly and nonspecifically to the polyanion and complete folding in the bound state.

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Figure 1: DNA accelerates the refolding of Arc.
Figure 2: Rate dependence on salt, PVS, and DNA concentration.
Figure 3: Urea and viscosity dependence.
Figure 4: Possible pathways for Arc refolding in the presence of polyanions (P).

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References

  1. Raumann, B.E., Brown, B.M. & Sauer, R.T. Curr. Opin. Struct. Biol. 4, 36–43 (1994).

    Article  CAS  Google Scholar 

  2. Breg, J.N., van Opheusden, J.H.J., Burgering, M.J., Boelens, R. & Kaptein, R. Nature 346, 586–589 (1990).

    Article  CAS  Google Scholar 

  3. Bonvin, A.M. et al. J. Mol. Biol. 236, 328–341 (1994).

    Article  CAS  Google Scholar 

  4. Raumann, B.E., Rould, M.A., Pabo, C.O., & Sauer, R.T. Nature 367, 75–757 (1994).

    Article  Google Scholar 

  5. Bowie, J.U. & Sauer, R.T. Biochemistry 28, 7139–7143 (1989).

    Article  CAS  Google Scholar 

  6. Milla, M.E. & Sauer, R.T. Biochemistry 33, 1125–1133 (1994).

    Article  CAS  Google Scholar 

  7. Jonsson, T., Waldburger, C.D. & Sauer, R.T. Biochemistry, 35, 4795–4802 (1996).

    Article  CAS  Google Scholar 

  8. Waldburger, C.D., Jonsson, T. & Sauer, R.T. Proc. Natl. Acad. Sci. USA 93, 2629–2634 (1996).

    Article  CAS  Google Scholar 

  9. Robinson, C.R. & Sauer, R.T. Biochemistry 35, 13878–13884 (1996).

    Article  CAS  Google Scholar 

  10. Tanford, C. Adv. Prot. Chem. 24, 1–95 (1970).

    CAS  Google Scholar 

  11. Becktel, W.J. & Schellman, J.A. Biolpolymers 26, 1859–1877 (1987).

    Article  CAS  Google Scholar 

  12. Matouschek, A. & Fersht, A.R. Proc. Natl. Acad. Sci., USA 90, 7814–7818 (1993).

    Article  CAS  Google Scholar 

  13. Milla, M.E., Brown, B.M., Waldburger, C.D. & Sauer, R.T. Biochemistry 34, 13914–13919 (1995).

    Article  CAS  Google Scholar 

  14. Neidhardt, F.C., Ingraham, J.L. & Schaechter, M. Physiology of the bacterial cell: A molecular approach. (Sinauer Associates, Sunderland, Massachusetts; 1990).

  15. Gittleman, M.S. & Matthews, C.R. Biochemistry 29, 7011–7020 (1990).

    Article  Google Scholar 

  16. Weiss, M.A. Biochemistry 29, 8020–8024 (1990).

    Article  CAS  Google Scholar 

  17. Rose, J. & Yanofsky, C. Proc. Natl. Acad. Sci. USA 71, 3134–3138 (1974).

    Article  CAS  Google Scholar 

  18. Metallo, S.J. & Schepartz, A. Nature Struct. Biol. 4, 115–117 (1997).

    Article  CAS  Google Scholar 

  19. Milla, M.E., Brown, B.M., & Sauer, R.T. Prot. Sci. 2, 2198–2205 (1993).

    Article  CAS  Google Scholar 

  20. Milla, M.E., Brown, B.M., & Sauer, R.T. Nature Struct. Biol. 1, 518–523 (1994).

    Article  CAS  Google Scholar 

  21. Brown, B.M., Milla, M.E., Smith, T.L. & Sauer, R.T. Nature Struct. Biol. 1, 164–168 (1994).

    Article  CAS  Google Scholar 

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Acknowledgements

D.R. and T.J. contributed equally to this work. Supported by NIH grants and a postdoctoral grant from the Damon Runyon/Walter Winchell Cancer Fund (D.R.). We thank B. Brown, M. Milla, and C. Robinson for mutant proteins, and F. Solomon for helpful discussions and comments on the manuscript.

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Author notes

  1. Dionisios Rentzeperis

    Present address: 3D Pharmaceuticals, Exton, Pennsylvania, USA

  2. Thorlakur Jonsson

    Present address: DeCode Genetics, Reykjavik, Iceland

Authors and Affiliations

  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139-4703, Massachusetts, USA

    Dionisios Rentzeperis, Thorlakur Jonsson & Robert T. Sauer

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  1. Dionisios Rentzeperis
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  2. Thorlakur Jonsson
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  3. Robert T. Sauer
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Correspondence to Robert T. Sauer.

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Rentzeperis, D., Jonsson, T. & Sauer, R. Acceleration of the refolding of Arc repressor by nucleic acids and other polyanions. Nat Struct Mol Biol 6, 569–573 (1999). https://doi.org/10.1038/9353

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